4.5 Article

Increasing circulating exosomes-carrying TRPC5 predicts chemoresistance in metastatic breast cancer patients

Journal

CANCER SCIENCE
Volume 108, Issue 3, Pages 448-454

Publisher

WILEY
DOI: 10.1111/cas.13150

Keywords

Breast cancer; chemoresistance; exosome; prediction; transient receptor potential canonical 5

Categories

Funding

  1. Jiangsu Province Clinical Medical Science and Technology Specialized Research Fund [BL2014019]
  2. Natural Science Foundation of Jiangsu Province of China [BK20150162]
  3. Wuxi Science and Technology Bureau [Z201401]
  4. Key Program from Wuxi Hospital Management Center [YGZXG1406]
  5. Scientific and Technological Development Fund from Wuxi Science and Technology Bureau [CSE31N1419]
  6. National Natural Science Foundation of China [81541156]

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Chemoresistance, the major obstacle in breast cancer chemotherapy, results in unnecessary chemotherapy and wasting of medical resources. No feasible method has been available to predict chemoresistance before chemotherapy. In our previous study, elevated expression of transient receptor potential channel TRPC5 was found to be an essential element for chemoresistance in breast cancer cells, and it was determined that it could be transferred to chemosensitive breast cancer cells through releasing extracellular vesicles (EV) containing TRPC5 from chemoresistant cells, resulting in acquired chemoresistance. Exosomes, a type of EV, are secreted membrane-enclosed vesicles of 50-150-nm diameter. In this study we found that circulating exosomes in peripheral blood from breast cancer patients carried TRPC5. In the present study, circulating exosome-carrying TRPC5 (cirExo-TRPC5) level was significantly correlated with TRPC5 expression level in breast cancer tissues and tumor response to chemotherapy. Furthermore, increased cirExo- TRPC5 level after chemotherapy preceded progressive disease (PD) based on imaging examination and strongly predicted acquired chemoresistance. Taken together, our study demonstrated that cirExo-TRPC5 might act as a noninvasive chemoresistance marker and might serve as an adjuvant to the current imaging examination-based chemoresistance.

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